Erbe AK, Diccianni MB, Mody R, Naranjo A, Zhang FF, Birstler J, Kim K, Feils AS, Hung JT, London WB, Shulkin BL, Mathew V, Parisi MT, Servaes S, Asgharzadeh S, Maris JM, Park J, Yu AL, Sondel PM, Bagatell R. KIR/KIR-ligand genotypes and clinical outcomes following chemoimmunotherapy in patients with relapsed or refractory neuroblastoma: a report from the Children’s Oncology Group. J Immunother Cancer. 2023 Feb;11(2). doi: 10.1136/jitc-2022-006530. PubMed PMID: 36822669; PubMed Central PMCID: PMC9950969.
Study ID Citation
Abstract
In the Children’s Oncology Group ANBL1221 phase 2 trial for patients with first relapse/first declaration of refractory high-risk neuroblastoma, irinotecan and temozolomide (I/T) combined with either temsirolimus (TEMS) or immunotherapy (the anti-GD2 antibody dinutuximab (DIN) and granulocyte macrophage colony stimulating factory (GM-CSF)) was administered. The response rate among patients treated with I/T/DIN/GM-CSF in the initial cohort (n=17) was 53%; additional patients were enrolled to permit further evaluation of this chemoimmunotherapy regimen. Potential associations between immune-related biomarkers and clinical outcomes including response and survival were evaluated. Patients were evaluated for specific immunogenotypes that influence natural killer (NK) cell activity, including killer immunoglobulin-like receptors (KIRs) and their ligands, Fc gamma receptors, and NCR3. Total white cells and leucocyte subsets were assessed via complete blood counts, and flow cytometry of peripheral blood mononuclear cells was performed to assess the potential association between immune cell subpopulations and surface marker expression and clinical outcomes. Appropriate statistical tests of association were performed. The Bonferroni correction for multiple comparisons was performed where indicated.